The purpose of this phase II study is to find out what effects cabozantinib (XL184) has, good and/or bad, in patients whose tumors one of the following gene changes RET, ROS1, or NTRK fusion, or increased MET or AXL activity.
A phase II study looks at how effective a medication is at treating a specific type of cancer and collects information on the side effects of the study treatment.
RET, ROS1, or NTRK fusion or increased MET or AXL activity gene leads to lung cancer cell growth. Cabozantinib is an oral medicine that inhibits of RET, ROS1, NTRK, MET, and AXL. In addition, this drug interferes with other cell pathways that also cause cancer cells to grow, form new blood vessels, and spread to other organs of the body. The goal of using cabozantinib is to shrink the cancer and to prevent it from growing
Cabozantinib has been studied and shown to cause cancer shrinkage in other cancers such as medullary thyroid cancer and prostate cancer. We thus have a good idea of what side-effects it causes and can anticipate them.
The subject has a pathologic diagnosis of non-small cell lung carcinoma that is metastatic or unresectable.
Group A: KIF5B/RET or related variant RET fusions.
Group B: any of the following aberrations
Group C: ROS1 fusion
Any type of systemic anticancer agent (including investigational) within 3 weeks of first dose of study treatment, or within 5 half-lives of the agent whichever is shorter. Subjects on LHRH or GnRH agonists may be maintained on these agents.
Prior treatment with cabozantinib
Radiation therapy for bone or brain metastasis within 2 weeks, any other external radiation therapy within 4 weeks of first dose of study drug. Systemic treatment with radionuclides within 4weeks. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs.
Single group
Cabozantinib
DrugPatients will receive cabozantinib at an initial dose of 60 mg orally daily. The drug is taken continuously over a period of 28 days (4 weeks), which constitutes one treatment cycle. Dose modifications for drug toxicity are permitted as per a prescribed algorithm. During the Treatment Period subjects will receive cabozantinib until either disease progression, the occurrence of unacceptable drug-related toxicity or for other reason(s) for subject withdrawal.
objective response rate (ORR) (Group A)
by RECIST v1.1 criteria to cabozantinib in patients with advanced NSCLC who have tested positive for RET Fusion
objective response rate (ORR) (Group B)
by RECIST v1.1 criteria to cabozantinib in patients with advanced NSCLC whose tumors test positive for a ROS1 or NTRK fusion or MET or AXL overexpression, amplification, or mutation.
progression-free survival (PFS) (Group A)
Progression-free (PFS) and overall survival (OS) will be calculated using Kaplan-Meyer estimators starting from the time of treatment initiation. For PFS, patients alive without evidence of progression at the end of the study will be censored at the time of the last available follow-up. For OS, patients alive at the end of the study will be censored at the time of the last available follow-up.
overall survival (OS) (Group A)
Progression-free (PFS) and overall survival (OS) will be calculated using Kaplan-Meyer estimators starting from the time of treatment initiation. For PFS, patients alive without evidence of progression at the end of the study will be censored at the time of the last available follow-up. For OS, patients alive at the end of the study will be censored at the time of the last available follow-up.
safety (Group A, B, C & D)
Observed toxicities will be individually tabulated according to CTCAE version 4.0 and summarized using descriptive statistics.
progression-free survival (PFS) (Group B, C & D)
Progression-free (PFS) and overall survival (OS) will be calculated using Kaplan-Meyer estimators starting from the time of treatment initiation. For PFS, patients alive without evidence of progression at the end of the study will be censored at the time of the last available follow-up. For OS, patients alive at the end of the study will be censored at the time of the last available follow-up with advanced NSCLCs whose tumors test positive for a ROS1 or NTRK fusion or MET or AXL overexpression or amplification who were treated with cabozantinib.
objective response rate (ORR) (Group D)
by RECIST v1.1 criteria to cabozantinib in patients with advanced NSCLC who have tested positive for RET Fusion
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Memorial Sloan Kettering Cancer Center
Lead sponsor
Exelixis
Collaborator
